Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with RITUXAN, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RITUXAN. Discontinue RITUXAN and concomitant medications in the event of HBV reactivation

Warnings and Precautions

Tumor Lysis Syndrome

Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12−24 hours after the first infusion of RITUXAN in patients with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden, confers a greater risk of TLS. Administer aggressive intravenous hydration and anti hyperuricemic therapy in patients at high risk for TLS

Infections

Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of RITUXAN-based therapy. Discontinue RITUXAN for serious infections and institute appropriate anti infective therapy

Cardiovascular

Discontinue infusions for serious or life threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RITUXAN for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina

Renal

Severe, including fatal, renal toxicity can occur after RITUXAN administration in patients with NHL. Monitor closely for signs of renal failure and discontinue RITUXAN in patients with a rising serum creatinine or oliguria

Bowel Obstruction and Perforation

Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur

Immunization

The safety of immunization with live viral vaccines following RITUXAN therapy has not been studied and vaccination with live virus vaccines is not recommended

Laboratory Monitoring

Obtain complete blood counts (CBC) prior to each RITUXAN course

Additional Important Safety Information

The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and CLL were infusion reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials

The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials

Pregnancy: Category C. There are no adequate and well-controlled studies of rituximab in pregnant women

ECOG 1496 Trial

In first-line follicular or low-grade lymphoma patients who did not progress following CVP

RITUXAN post-induction therapy reduced the risk of progression, relapse, or death by 51%

ECOG 1496 TRIAL DESIGN1

*CVP=cyclophosphamide 1 g/m2 on Day 1; vincristine 1.4 mg/m2 on Day 1; prednisone 100 mg/m2 on Days 1–5. After the completion of 6 to 8 twenty-one–day cycles of CVP, patients achieving a CR, PR, or SD were randomized to receive no further treatment or to receive post-induction therapy with RITUXAN. Beginning 4 weeks after completion of induction therapy, patients randomized to RITUXAN received 1 cycle of 4 weekly treatments with 375 mg/m2 RITUXAN, every 6 months for up to 4 cycles.1

B-CELL DEPLETION AFTER RITUXAN MONOTHERAPY IN THE McLAUGHLIN TRIAL2

In the McLaughlin monotherapy trial in relapsed or refractory, low-grade or follicular NHL2:

RITUXAN 375 mg/m2 was administered once weekly for 4 weeks

B cells were rapidly depleted after 4 doses of RITUXAN

Recovery began at 6 months and returned to baseline levels by 12 months after completion of a 4-week course of RITUXAN monotherapy

B-cell depletion observed in the McLaughlin trial formed the basis for the ECOG 1496 dosing strategy following first-line CVP induction in low-grade NHL2

The ECOG 1496 trial included both low- and high-risk patients

PATIENT CHARACTERISTICS3

Baseline characteristics

CVP→R
(n=162)

CVP→Obs
(n=160)

Age range (years)

26-84

26-85

Median age

58

55

Elevated LDH (>1×ULN)

24%

21%

Ann Arbor Stage

I/II III/IV

1%
99%

0%
100%

ECOG performance status

01

72%
28%

60%
40%

Bulky disease (>10cm)

19%

24%

Number of extranodal sites

01≥2

19%
52%
30%

15%
43%
42%

CRF-derived IPI score†

0-1 2 3-4

38%
41%
21%

36%
43%
21%

†The IPI score, which ranged from 0 to 5, was derived by assigning 1 point for each of the following risk factors: >60 years of age, Ann Arbor Stage III or IV, extranodal disease involvement at >1 site, ECOG performance status ≥2, and elevated LDH.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with RITUXAN, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RITUXAN. Discontinue RITUXAN and concomitant medications in the event of HBV reactivation

Warnings and Precautions

Tumor Lysis Syndrome

Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12−24 hours after the first infusion of RITUXAN in patients with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden, confers a greater risk of TLS. Administer aggressive intravenous hydration and anti hyperuricemic therapy in patients at high risk for TLS

Infections

Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of RITUXAN-based therapy. Discontinue RITUXAN for serious infections and institute appropriate anti infective therapy

Cardiovascular

Discontinue infusions for serious or life threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RITUXAN for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina

Renal

Severe, including fatal, renal toxicity can occur after RITUXAN administration in patients with NHL. Monitor closely for signs of renal failure and discontinue RITUXAN in patients with a rising serum creatinine or oliguria

Bowel Obstruction and Perforation

Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur

Immunization

The safety of immunization with live viral vaccines following RITUXAN therapy has not been studied and vaccination with live virus vaccines is not recommended

Laboratory Monitoring

Obtain complete blood counts (CBC) prior to each RITUXAN course

Additional Important Safety Information

The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and CLL were infusion reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials

The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials

Pregnancy: Category C. There are no adequate and well-controlled studies of rituximab in pregnant women

Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with RITUXAN, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RITUXAN. Discontinue RITUXAN and concomitant medications in the event of HBV reactivation

Warnings and Precautions

Tumor Lysis Syndrome

Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12−24 hours after the first infusion of RITUXAN in patients with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden, confers a greater risk of TLS. Administer aggressive intravenous hydration and anti hyperuricemic therapy in patients at high risk for TLS

Infections

Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of RITUXAN-based therapy. Discontinue RITUXAN for serious infections and institute appropriate anti infective therapy

Cardiovascular

Discontinue infusions for serious or life threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RITUXAN for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina

Renal

Severe, including fatal, renal toxicity can occur after RITUXAN administration in patients with NHL. Monitor closely for signs of renal failure and discontinue RITUXAN in patients with a rising serum creatinine or oliguria

Bowel Obstruction and Perforation

Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur

Immunization

The safety of immunization with live viral vaccines following RITUXAN therapy has not been studied and vaccination with live virus vaccines is not recommended

Laboratory Monitoring

Obtain complete blood counts (CBC) prior to each RITUXAN course

Additional Important Safety Information

The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and CLL were infusion reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials

The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials

Pregnancy: Category C. There are no adequate and well-controlled studies of rituximab in pregnant women